New resin systems for dental restorative materials

ABSTRACT

The disclosure provides a new photopolymerizable resin system for dental restorative materials. The resin system utilizes a thiol-ene component as the reactive diluent in dimethacrylate systems. The ternary resin system comprises a thiol monomer, an ene monomer and a dimethacrylate monomer. Use of an off-stoichiometric ratio of thiol:ene functional groups in favor of excess thiols results in enhanced overall functional group conversion, improved polymer mechanical properties, and reduced shrinkage stress of the ternary system when compared to either traditional dimethacrylate or thiol-ene resin systems.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 12/415,783, filed Mar. 31, 2009, which is a continuation-in-part ofU.S. application Ser. No. 10/576,635, with a §371 date of Apr. 21, 2006,now U.S. Pat. No. 7,838,571, which is a U.S. National Phase applicationof PCT/US04/34969, filed Oct. 22, 2004, which claims the benefit of U.S.provisional application No. 60/513,900, filed Oct. 22, 2003, each ofwhich is incorporated by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The invention was made with government support under grant numbersDE010959 and DE018233 awarded by the National Institutes of Health. Thegovernment has certain rights in the invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The disclosure provides a new photopolymerizable resin system for dentalrestorative materials. The resin system utilizes a thiol-ene componentas the reactive diluent in dimethacrylate systems. The ternary resinsystem comprises a thiol monomer, an ene monomer and a dimethacrylatemonomer. Use of an off-stoichiometric ratio of thiol:ene functionalgroups in favor of excess thiols results in enhanced overall functionalgroup conversion, improved polymer mechanical properties, and reducedshrinkage stress of the ternary system when compared to eithertraditional dimethacrylate or thiol-ene resin systems.

2. Background Art

Currently, most commercial photocurable dental restorative resins arebased on dimethacrylates and the reaction mechanism is throughchain-growth free radical polymerization. Existing dimethacrylatesystems are popular for fillings and other dental prostheses because oftheir esthetic merit and “cure-on-command” feature. These formulationshave resulted in significant advancements in the field of dentistry.

Such dental restorative materials are often mixed with 45 to 85% byweight (wt %) silanized filler compounds such as barium, strontium,zirconia silicate and/or amorphous silica to match the color and opacityto a particular use or tooth. The filler is typically in the form ofparticles with a size ranging from 0.01 to 5.0 micrometers.

The photocurable restorative materials are often sold in separatesyringes or single-dose capsules of different shades. If provided in asyringe, the user dispenses (by pressing a plunger or turning a screwadapted plunger on the syringe) the necessary amount of restorativematerial from the syringe. Then the material is placed directly into thecavity, mold, or location of use. If provided as a single-dose capsule,the capsule is placed into a dispensing device that can dispense thematerial directly into the cavity, mold, etc. After the restorativematerial is placed, it is photopolymerized or cured by exposing therestorative material to the appropriate light source. The resultingcured polymer may then be finished or polished as necessary withappropriate tools. Such dental restoratives can be used for directanterior and posterior restorations, core build-ups, splinting andindirect restorations including inlays, onlays and veneers.

Although easy to use, these dimethacrylate systems have severaldrawbacks and there are a number of properties of the resin chemistrythat, if improved upon, would increase the performance, longevity andbiocompatibility of composite restorations (Sakaguchi et al., DentalMaterials 21:43-46, 2005; Dauvillier et al., Journal of BiomedicalMaterials Research 58(1):16-26, 2001; Dauvillier et al., Journal ofDental Research 79(3):818-823, 2000; Yourtee et al., In Vitro Toxicology10:245-251, 1997). The most significant shortcomings ofmethacrylate-based resins are high volumetric shrinkage (Ferracane,Dental Materials 21:36-42, 2005), high polymerization stress (Braga etal., Dental Materials 21:962-970, 2005; Lu et al., Dental Materials,21(12):1129-1136, 2005; Braga and Ferracane, Journal of Dental Research81:114-118, 2002) and low functional group conversion (Darmani andAl-Hiyasat, Dental Materials 22:353-358, 2006; Sasaki et al., Journal ofMaterials Science: Materials in Medicine 16:297-300, 2005; Pulgar etal., Environmental Health Perspectives 108:21-27, 2000). The chaingrowth polymerization mechanism results in long chains and thereforeearly gelation which contributes to both volume shrinkage and shrinkagestress. The current systems typically only reach a final double bondconversion of 55 to 75%, which not only contributes to the insufficientwear resistance and mechanical properties, but also jeopardizes thebiocompatibility of the composites due to the leachable unreactedmonomers. Additionally, the residual monomer left in the restorationafter curing is extractable and may leach out of the restoration andinto the body, with unknown consequences (Sasaki et al., 2005; Pulgar etal., 2000). There is concern that residual monomers may cause allergicreactions and sensitization in patients (Theilig et al., Journal ofBiomedical Materials Research 53(6):632-639, 2000). There is also reasonto believe that release of the most common reactive diluent, triethyleneglycol dimethacrylate (TEGDMA), may also contribute to local andsystemic adverse effects by dental composites (Hansel et al., Journal ofDental Research 77(1):60-67, 1998; Englemann et al., Journal of DentalResearch 80(3):869-875, 2001; Schweikl and Schmalz, MutationResearch-Genetic Toxicology and Environmental Mutagenesis 438:71-78,1999; Darmani and Al-Hiyasat, 2006).

Upon polymerization, shrinkage stresses transferred to the tooth cancause deformation of the cusp or enamel microcracks (Davidson andFeilzer, J Dent. 25:435-440, 1997; Suliman et al., Journal of DentalResearch 72(11):1532-1536, 1993a; Suliman et al., Dental Materials9(1):6-10, 1993b), and stress at the tooth-composite interface may causeadhesive failure, initiation of microleakage and recurrent caries. Inaddition, significant increases in volumetric shrinkage and shrinkagestress are experienced when the double bond conversion is increased toreduce the leachable monomer (Lu et al., Journal of Biomedical MaterialsResearch Part B-Applied Biomaterials, 71B:206-213, 2004). This trade-offof conversion and shrinkage has been an inherent problem with compositerestorative materials since their inception.

Recently, thiol-enes have been investigated as alternatives todimethacrylate dental restorative materials (Lu et al., 2005; Cramer etal., “Investigation of Thiol-Ene Based Systems as Dental RestorativeMaterials” to be submitted to Dental Materials. 2009.). The reactionsproceed via a step growth addition mechanism that comprises the additionof a thiyl radical through a vinyl functional group and subsequent chaintransfer to a thiol, regenerating the thiyl radical (Jacobine, A. F.Radiation Curing in Polymer Science and Technology III, PolymerisationMechanisms; Fouassier, J. D.; Rabek, J. F., Ed.; Elsevier AppliedScience, London, 1993; Chapter 7, 219; Hoyle et al., Journal of PolymerScience: Part A: Polymer Chemistry, 2004, 42, 5301-5338; Cramer andBowman, Journal of Polymer Science. Part A. Polymer Chemistry, 2001, 39(19), 3311; Cramer et al., Macromolecules, 2003a, 36 (12), 4631; Crameret al., Macromolecules, 2003b, 36 (21), 7964; Reddy et al.Macromolecules, 2006, 39(10), 3673). The step-growth polymerizationmechanism results in shorter polymer chains and delayed gelation,resulting in reduced volume shrinkage and shrinkage stress. It is wellknown that in thiol-ene step growth polymerizations, the thiol and enecomponents must be present in a 1:1 stoichiometric ratio of functionalgroups to achieve complete conversion and maximize polymer mechanicalproperties (Morgan et al., J. Polym. Sci., A, Polym. Chem. 627, 1977;Jacobine et al., Journal of Applied Polymer Science 45(3):471-485, 1992;Cramer and Bowman, 2001; Hoyle et al., 2004). The high functional groupconversion of thiol-ene polymers significantly mitigates the problemsassociated with current dimethacrylate resin systems which areassociated with incomplete double bond conversion. Besides the impact ofthe polymerization mechanism on the gel point conversion and networkformation, the thiol-ene systems have advantageous curing kineticsdemonstrating rapid polymerization rates, high overall functional groupconversion, and little sensitivity to oxygen inhibition (Lu et al.,Dental Materials, 21(12), 2005, 1129-1136; Cramer et al.,Macromolecules, 35, 5361, 2002; Hoyle et al., 2004).

Most importantly for dental restorative materials, thiol-enes exhibitreduced shrinkage and shrinkage stress due to the step growth mechanismand delayed gel point conversion (Chiou et al., Macromolecules, 1997,30, 7322; Lu et al., 2005). As a result of the delayed gel point, muchof the shrinkage occurs before gelation, which dramatically reduces theshrinkage stress in the final polymer material.

The thiol-ene polymerization has also demonstrated thicker curing depththan methacrylate based resin systems. This can reduce the patient'schair-time since one-step curing is feasible, especially for largecavity filling, where incremental filling has to be applied usingcurrent dental composite systems. In addition, the thick cure depth andlack of oxygen inhibition of thiol-ene systems leads to fewer fillingand curing steps during restorations, compared with the incrementalfilling technique using current dimethacrylate dental resin systems

Unfortunately, despite several advantages of the thiol-ene resin systemsfor use as dental restorative materials, previous studies have alsoshown that traditional binary thiol-ene systems exhibit mechanicalproperties that are not ideal; specifically low flexural modulus andstrength relative to dimethacrylate resins (Lu et al., 2005; Cramer etal., 2009). Thus, it is important to develop rapidly curing dentalrestorative materials with improved monomer conversion and mechanicalproperties, while concurrently reducing volumetric shrinkage andshrinkage stress.

SUMMARY OF THE INVENTION

The disclosure provides a photopolymerizable dental restorativecomposition comprising a methacrylate monomer, a thiol monomer and anene monomer. The composition comprises, relative to the total weight ofall polymerizable monomers, at least about 40% by weight of themethacrylate monomer; and at least about 10% by weight of combinedweight of the thiol monomer and an ene monomer; and wherein the molarratio of thiol functional groups from the thiol monomer relative to theene functional groups from the ene monomer is greater than about 1:1;preferably greater than about 1.5:1; more preferably greater than about1.75:1; more preferably greater than about 2:1.

In one embodiment, the composition of claim 1 further comprising aphotoinitiator selected from one or more of a visible light activatedphotoinitiator, and/or a UV light activated photoinitiator. In oneaspect, the photoinitiator is selected from (2,4,6-trimethyl benzoyl)phosphine oxide, camphorquinone, Bis9eta 5-2,4-cyclopentadien-1-yl)Bis[2,6-difluoro-3-(1H-pyrrol-1-yl)phenyl]titanium,1-hydroxy-cyclohexyl-phenylketone, and2,2-dimethoxy-2-phenylacetophenone. In another aspect the compositionfurther comprises a polymerization accelerator and/or a polymerizationinhibitor.

In one embodiment, the methacrylate-thiol-ene resin composition furthercomprises a filler in an amount of up to 90%; preferably 60 to 85% byweight with respect to the total weight of the filled composition.

In one aspect, the methacrylate-thiol-ene resin composition comprises 50to 80% by weight of the methacrylate monomer; and 20 to 50% by weight ofthe combined weight of the thiol monomer and the ene monomer. In anotheraspect, the methacrylate-thiol-ene resin composition comprises 60 to 70%by weight of the methacrylate monomer; and 30 to 40% by weight of thecombined weight of the thiol monomer and the ene monomer.

In another aspect, the methacrylate-thiol-ene resin compositioncomprises a methacrylate monomer that is a dimethacrylate monomer. Inspecific aspects, the methacrylate monomer is selected from ethyleneglycoldi(meth)acrylate, ethoxylated bisphenol-A dimethacrylate(EBPADMA), tetraethyleneglycoldi(meth)acrylate (TEGDMA), poly(ethyleneglycol) dimethacrylates, the condensation product of bisphenol A andglycidyl methacrylate, 2,2′-bis[4-(3-methacryloxy-2-hydroxypropoxy)-phenyl] propane (BisGMA), hexanediol di(meth)acrylate,tripropylene glycol di(meth)acrylate, butanediol di(meth)acrylate,neopentyl glycol di(meth)acrylate, diethylene glycol di(meth)acrylate,triethylene glycol di(meth) acrylate, dipropylene glycoldi(meth)acrylate, allyl (meth)acrylate. In one specific aspect, themethacrylate monomer is ethoxylated bisphenol-A dimethacrylate(EBPADMA).

In a further aspect, the methacrylate-thiol-ene resin compositioncomprises a thiol monomer selected from one or more of pentaerythritoltetramercaptopropionate (PETMP); 1-Octanethiol; Butyl3-mercaptopropionate; 2,4,6-trioxo-1,3,5-triazina-trig(triethyl-tris(3-mercapto propionate); 1,6-Hexanedithiol;2,5-dimercaptomethyl-1,4-dithiane, pentaerythritol tetramercaptoacetate,trimethylolpropane trimercaptoacetate, 2,3-dimercapto-1-propanol,2-mercaptoethylsulfide, 2,3-(dimercaptoethylthio)-1-mercaptopropane,1,2,3-trimercaptopropane, toluenedithiol, xylylenedithiol,1,8-octanedithiol, 1-hexanethiol and trimethylolpropanetris(3-mercaptopropionate), and glycol dimercaptopropionate. In aspecific aspect, the thiol monomer is pentaerythritoltetramercaptopropionate (PETMP).

In one aspect, the methacrylate-thiol-ene resin composition comprises anene monomer with two or more ene functional groups. In certain aspects,the ene monomer is selected from one or more ofTriallyl-1,3,5-triazine-2,4,6-trione (TATATO); Triethyleneglycol divinylether (TEGDVE); Trimethylolpropane diallyl ether; Dodecyl vinyl ether(DDVE); 1,6-heptadiyne; 1,7-octadiyne;bis-2,2-[4-(2-[norborn-2-ene-5-carboxylate]ethoxy)phenyl]propane(BPAEDN); 1,6-hexanediol di-(endo,exo-norborn-2-ene-5-carboxylate)(HDDN); trimethylolpropane tri-(norborn-2-ene-5-carboxylate) (TMPTN);pentaerythritoltri-(norborn-2-ene-5-carboxylate) (PTN3);pentaerythritoltetra-(norborn-2-ene-5-carboxylate) (PTN4);tricyclodecane dimethanol di-(endo, exo-norborn-2-ene-5-carboxylate)(TCDMDN); and di(trimethylolpropane)tetra-(norborn-2-ene-5-carboxylate)(DTMPTN). In one specific aspect, the ene monomer isTriallyl-1,3,5-triazine-2,4,6-trione (TATATO). In another specificaspect, the ene monomer is trimethylolpropanetri-(norborn-2-ene-5-carboxylate) (TMPTN).

In another embodiment, the disclosure provides a method of preparing ashaped dental prosthetic device for use in a human mouth, the methodcomprising dispensing a photopolymerizable composition comprising,relative to the total weight of all polymerizable monomers: at leastabout 40% by weight of a methacrylate monomer; and at least about 10% byweight of combined weight of a thiol monomer and an ene monomer; whereinthe molar ratio of thiol functional groups from the thiol monomerrelative to the ene functional groups from the ene monomer is greaterthan about 1:1; a photoinitiator; and a filler; shaping the compositioninto a form of the shaped dental prosthetic device; andphotopolymerizing the shaped composition. In one aspect, the methodutilizes a the methacrylate-thiol-ene resin composition wherein themolar ratio of the thiol functional groups to the ene functional groupsis greater than about 1.5:1.

In a further embodiment, the disclosure provides a photopolymerizabledental restorative composition comprising a methacrylate monomer and athiol monomer, wherein the composition comprises, relative to the totalweight of all polymerizable monomers at least 50% by weight of amethacrylate monomer; and wherein the balance of the polymerizablemonomers are thiol monomers. In one aspect, the methacrylate-thiolcomposition further comprises a photoinitiator.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows various methacrylate, thiol and ene monomers.

FIG. 2 shows methacrylate functional group conversion uponphotopolymerization of two methacrylate control systems and two ternarymethacrylate-thiol-ene resin systems.

FIG. 3 shows both methacrylate and ene (ene) functional group conversionutilizing a methacrylate-thiol-ene system with EBPADMA/PETMP:TATATO, ina 70/30 weight percent of methacrylate (EBPADMA) to thiol:ene(PETMP:TATATO). The 1:1; 2:1 and 3:1 ratios represent the molar ratio ofthiol (PETMP) to ene (TATATO) functional groups.

FIG. 4 shows methacrylate functional group conversion utilizing amethacrylate-thiol-ene system with EBPADMA/PETMP:TMPTN, in a 70/30weight percent of methacrylate (EBPADMA) to thiol:ene (PETMP:TMPTN). The1:1; 2:1 and 3:1 ratios represent the molar ratio of thiol (PETMP) toene (TMPTN) functional groups.

FIG. 5 shows Flexural Modulus of two methacrylate control resin systems(A, B), a methacrylate/thiol resin system (C), and fourmethacrylate/thiol/ene resin systems after photopolymerization.Formulations A-G are described in Table 3.

FIG. 6 shows Flexural Strength of two methacrylate control resin systems(A, B), a methacrylate/thiol resin system (C), and fourmethacrylate/thiol/ene resin systems after photopolymerization.Formulations A-G are described in Table 3.

FIG. 7 shows shrinkage stress and methacrylate conversion for controlmethacrylate and methacrylate/thiol systems upon polymerization.

FIG. 8 shows shrinkage stress and methacrylate conversion for variousEBPADMA/PETMP/TATATO resin systems compared to dimethacrylate controlsystems.

FIG. 9 shows shrinkage stress and methacrylate conversion for variousEBPADMA/PETMP/TMPTN resin systems compared to dimethacrylate controlsystems.

FIG. 10 shows Flexural Strength for two methacrylate-thiol-ene systemswith various filler formulations from Example 5.

FIG. 11 shows Flexural Modulus for two methacrylate-thiol-ene systemswith various filler formulations from Example 5.

FIG. 12 shows Microhardness for two methacrylate-thiol-ene systems withvarious filler formulations from Example 5.

DETAILED DESCRIPTION OF THE INVENTION

The disclosure provides a new photopolymerizable resin system for dentalrestorative materials. The resin system utilizes a thiol-ene componentas the reactive diluent in dimethacrylate systems. The ternary resinsystem comprises a thiol monomer, an ene monomer and a dimethacrylatemonomer. Although traditional thiol-ene systems utilize a 1:1stoichiometric ratio of ene to thiol functional groups for optimumconversion, it is herein disclosed that use of an off-stoichiometricratio of thiol:ene functional groups in favor of excess thiols resultsin further enhanced overall functional group conversion, improvedpolymer mechanical properties, and reduced shrinkage stress of theternary system when compared to either traditional dimethacrylate orthiol-ene resin systems.

As used herein, the following definitions shall apply unless otherwiseindicated.

The term “aliphatic” or “aliphatic group” as used herein means astraight-chain or branched hydrocarbon chain that is completelysaturated or that contains one or more units of unsaturation, or amonocyclic hydrocarbon or bicyclic hydrocarbon that is completelysaturated or that contains one or more units of unsaturation, but whichis not aromatic (also referred to herein as “carbocycle” or“cycloalkyl”), that has a single point of attachment to the rest of themolecule wherein any individual ring in said bicyclic ring system has3-7 members. F or example, suitable aliphatic groups include, but arenot limited to, linear or branched or alkyl, alkenyl, alkynyl groups andhybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or(cycloalkyl)alkenyl.

The terms “alkyl” and “alkoxy,” used alone or as part of a larger moietyinclude both straight and branched carbon chains. The terms “alkenyl”and “alkynyl” used alone or as part of a larger moiety shall includeboth straight and branched carbon chains.

The terms “haloalkyl,” “haloalkenyl” and “haloalkoxy” means alkyl,alkenyl or alkoxy, as the case may be, substituted with one or morehalogen atoms. The term “halogen” or “halo” means F, Cl, Br or I.

The term “heteroatom” means nitrogen, oxygen, or sulfur and includes anyoxidized form of nitrogen and sulfur, and the quaternized form of anybasic nitrogen.

The terms “mercapto” or “thiol” refer to an —SH substituent, or are usedto designate a compound having an —SH substituent.

The term “aryl” used alone or in combination with other terms, refers tomonocyclic, bicyclic or tricyclic carbocyclic ring systems having atotal of five to fourteen ring members, wherein at least one ring in thesystem is aromatic and wherein each ring in the system contains 3 to 8ring members. The term “aryl” may be used interchangeably with the term“aryl ring”.

The term “aralkyl” refers to an alkyl group substituted by an aryl. Theterm “aralkoxy” refers to an alkoxy group. The term “heterocycloalkyl,”“heterocycle,” “heterocyclyl” or “heterocyclic” as used herein meansmonocyclic, bicyclic or tricyclic ring systems having five to fourteenring members in which one or more ring members is a heteroatom, whereineach ring in the system contains 3 to 7 ring members and isnon-aromatic.

The term “monomer” refers to any discreet chemical compound of anymolecular weight.

The term “about” refers to +/−10% of the unit value provided.

Thiol bearing monomers suitable for embodiments of the present inventioninclude any monomer having thiol (mercaptan or “SH”) functional groups.Thiols are any of various organic compounds having the general formulaRSH which are analogous to alcohols but in which sulfur replaces theoxygen of the hydroxyl group. Suitable thiol monomers have one orpreferably more functional thiol groups and be of any molecular weight.In one aspect, the thiol monomer may be selected from one or more ofaliphatic thiols, thiol glycolate esters, thiol propionate esters.Examples of suitable thiol bearing monomers include: pentaerythritoltetramercaptopropionate (PETMP); 1-Octanethiol; Butyl3-mercaptopropionate; 2,4,6-trioxo-1,3,5-triazina-triy(triethyl-tris(3-mercapto propionate); 1,6-Hexanedithiol;2,5-dimercaptomethyl-1,4-dithiane, pentaerythritol tetramercaptoacetate,trimethylolpropane trimercaptoacetate, 2,3-dimercapto-1-propanol,2-mercaptoethylsulfide, 2,3-(dimercaptoethylthio)-1-mercaptopropane,1,2,3-trimercaptopropane, toluenedithiol, xylylenedithiol,1,8-octanedithiol, 1-hexanethiol (Sigma-Aldrich, Milwaukee, Wis.); andtrimethylolpropane tris(3-mercaptopropionate), and glycoldimercaptopropionate (Evans Chemetics LP, Iselin, N.J.).

Monomers having “-ene” or vinyl functional groups suitable forembodiments of the present invention include any monomer having one, orpreferably more functional vinyl groups, i.e., reacting “C═C” or “C≡C”groups. The ene monomer can be selected from one or more compoundshaving vinyl functional groups. Vinyl functional groups can be selectedfrom, for example, vinyl ether, vinyl ester, allyl ether, norbornene,diene, propenyl, alkene, alkyne, N-vinyl amide, unsaturated ester,N-substituted maleimides, and styrene moieties. Examples of suitable enemonomers include Triallyl-1,3,5-triazine-2,4,6-trione (TATATO);Triethyleneglycol divinyl ether (TEGDVE); Trimethylolpropane diallylether; 1,6-heptadiyne; 1,7-octadiyne; and Dodecyl vinyl ether (DDVE) andnorbornene monomers. In one specific aspect, the ene monomer is selectedfrom Triallyl-1,3,5-triazine-2,4,6-trione (TATATO), 1-Octanethiol1,6-hexanedithiol triethyleneglycol divinyl ether (TEGDVE), and Dodecylvinyl ether (DDVE). In one preferred aspect, the ene monomer istriallyl-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (TATATO).

In one aspect, the ene monomer is a norbornene monomer. A “norbornenemonomer” refers to any compound having a discrete chemical formula andhaving two or more norbornene pendent groups, or a reactive oligomer, orreactive polymer, or pre-polymer, having at least one, but preferablytwo or more norbornene groups. Suitable norbornene monomers includebis-2,2-[4-(2-[norborn-2-ene-5-carboxylate]ethoxy)phenyl]propane(BPAEDN), 1,6-hexanediol di-(endo,exo-norborn-2-ene-5-carboxylate)(HDDN),2-((bicyclo[2.2.1]hept-5-enecarbonyloxy)methyl)-2-ethylpropane-1,3-diylbis(bicyclo[2.2.1]hept-5-ene-2-carboxylate) (trimethylolpropanetri-(norborn-2-ene-5-carboxylate); TMPTN),pentaerythritoltri-(norborn-2-ene-5-carboxylate) (PTN3), pentaerythritoltetra-(norborn-2-ene-5-carboxylate) (PTN4), tricyclodecane dimethanoldi-(endo, exo-norborn-2-ene-5-carboxylate) (TCDMDN), anddi(trimethylolpropane)tetra-(norborn-2-ene-5-carboxylate) (DTMPTN).These norbornenes may be synthesized, for example, by the methods inCarioscia et al. J. Polymer Sci.: Part A: Polymer Chemistry 45,5686-5696 (2007), “Thiol-norbornene materials: Approaches to develophigh Tg thiol-ene polymers”, which is incorporated herein by reference.Certain other norbornene monomers may be prepared by the methods ofJacobine et al., 1992, Journal of Applied Polymer Science, 45(3),471-485 which is incorporated herein by reference. In one preferredaspect, the ene monomer is the norbornene monomer trimethylolpropanetri-(norborn-2-ene-5-carboxylate) (TMPTN).

The term “methacrylate monomer” refers to a discrete chemical compoundwhich is an ester of methacrylic acid. Methacrylate monomers suitablefor embodiments the present invention include any monomer having one orpreferably two or more methacrylate moieties. In one embodiment, themethacrylate monomer is a dimethacrylate monomer. As used herein, a“dimethacrylate monomer” is a monomer having two methacrylate moietiesper molecule. The methacrylate monomer is selected from one or moredimethacrylate monomers. Unless otherwise specified or implied, the term“(meth)acrylate” or “methacrylate” includes both the methacrylate andthe analogous acrylate. Examples of suitable dimethacrylate monomersinclude alkyldiol dimethacrylates: ethylene glycoldi(meth)acrylate,ethoxylated bisphenol-A dimethacrylate (EBPADMA), tetraethyleneglycoldi(meth)acrylate (TEGDMA), poly(ethylene glycol) dimethacrylates, thecondensation product of bisphenol A and glycidyl methacrylate,2,2′-bis[4-(3-methacryloxy-2-hydroxy propoxy)-phenyl] propane (BisGMA),hexanediol di(meth)acrylate, tripropylene glycol di(meth)acrylate,butanediol di(meth)acrylate, neopentyl glycol di(meth)acrylate,diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, dipropylene glycol di(meth)acrylate, allyl (meth)acrylate andderivatives thereof. In one preferred aspect, the methacrylate monomeris selected from2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BisGMA),ethoxylated bisphenol-A dimethacrylate (EBPADMA), and triethylene glycoldimethacrylate (TEGDMA).

Methacrylate systems polymerize via a chain growth homopolymerizationmechanism. In contrast, thiol-ene polymerization reactions proceed via astep growth addition mechanism that entails the addition of a thiylradical through a vinyl functional group and subsequent chain transferto a thiol, regenerating the thiyl radical (Jacobine et al., 1993; Hoyleet al., 2004; Cramer and Bowman, 2001; Cramer et al., 2003a; Cramer etal., 2003b; Reddy et al. Macromolecules, 2006, 39(10), 3681).Traditional binary thiol-ene systems utilize ene monomers that are nothomopolymerizable. Therefore, it is well known that in thiol-ene stepgrowth polymerizations, the thiol and ene components must be present ina 1:1 stoichiometric ratio of functional groups to achieve completeconversion and maximize polymer mechanical properties (Morgan et al.,1977; Jacobine et al., 1992; Cramer and Bowman 2001; Hoyle et al.,2004).

Previous experiments utilizing methacrylate-thiol and acrylate-thiolsystems have shown that methacrylate and acrylate functional groups arepreferentially consumed due to their participation in both step andchain growth addition reactions (Cramer and Bowman 2001; Lee, et al.,Macromolecules, 40(5), 1466, 2007; Lecamp et al., Polymer 2001, 42,2727). However, to date, only 1:1 thiol-ene stoichiometry has beeninvestigated in acrylate-thiol-ene and methacrylate-thiol-ene systems(Senyurt et al., Macromolecules 2007, 40(14), 4901-4909; Wei et al.,Journal of Polymer Science Part A-Polymer Chemistry 2007, 45(5),822-829.; Lee et al., Macromolecules, 40(5), 2007, 1466; Lee et al.,2007b; Cramer et al., 2009). Low ene conversion has been reported inthese systems in the cases where both (meth)acrylate and ene functionalgroup conversions have been resolved in FTIR (Lee et al., 2007; Crameret al., 2009). These results indicate that in ternary(meth)acrylate-thiol-ene systems a 1:1 thiol-ene ratio is not optimum.The thiol functional groups can react with both ene and methacrylatefunctional groups. However, the ene functional groups typically onlyreact with thiol functional groups. Therefore, when a 1:1 ratio isutilized the thiol functional groups become a limiting reagent resultingin the ene functional groups achieving a relatively low overallconversion.

The flexural strength of the resin systems should be equivalent to, orhigher, than the methacrylate controls to ensure that the materials arestrong enough to function as a tooth. However, the highest flexuralmodulus value is not necessarily desired. A material with a very highmodulus would be brittle and could shatter upon high impact withoutabsorbing any of the pressure. A material with a very low modulus wouldbe too soft and lack the toughness to act as a tooth. The results of theflexural testing show that the methacrylate-thiol-ene systems are ableto function as a tooth with a good flexural modulus and increasedflexural strength over the controls.

The ternary methacrylate-thiol-ene systems exhibit an increasedconversion and depth of cure over the methacrylate controls, while stillexperiencing less volumetric shrinkage and shrinkage stress, along withdecreased water solubility and sorption. The increased conversions notonly strengthen important mechanical and wear resistance properties, butthe biocompatibility of the systems will be improved for the ternarysystems. The decrease in volume shrinkage and shrinkage stress willincrease the longevity of the material for dental restorations.

As the ratio of thiol-to-ene in the ternary systems is increased, thematerials maintain equivalent mechanical properties while experiencingimprovements in other properties. The increased depth of cure andreduction in shrinkage stress may not be statistically significant, butconversion and volumetric shrinkage are improved with increases in thiolcontent. The increase in both methacrylate and allyl ether conversioncan be attributed to the fact the thiol functional groups can react withboth methacrylates and allyl ethers, but the allyl ether functionalgroups can react only with the thiol. Therefore if the amount of thioland allyl ether in a system is stoichiometric, the thiols are consumedby methacrylates and allyl ethers and become the limiting reagent in thethiol-ene reaction. This results in a low allyl ether functional groupconversion. As the ratio of thiol-to-ene is increased from 1:1 to 3:1,the allyl ether conversion is more than doubled along with a 7% increasein the methacrylate conversion.

As the thiol-to-ene ratio is increased to 3:1, there is also a nearly20% decrease in the volumetric shrinkage of the ternary system. Volumeshrinkage is proportional to double bond conversion only and is notdependent on thiol group conversion; therefore as the thiolconcentration is increased there are fewer double bond groups availablefor volume shrinkage (Lu et al., Journal of Dental Research 84:822-826,2005).

The improved mechanical properties, depth of cure, and water sorptionand solubility with reduced volume shrinkage and shrinkage stress maketernary methacrylate/thiol-ene systems superior to systems based on abulk dimethacrylate resin. The significant increase in functional groupconversion and the decrease in volumetric shrinkage exhibited bymethacrylate-thiol-ene ternary systems with an off-stoichiometric ratioof thiol-to-ene results in a system that compensates for shortcomings ofmethacrylate-based composites and makes methacrylate-thiol-ene systemsattractive as dental restorative materials.

The disclosure provides ternary (meth)acrylate-thiol-ene polymer resinsystems where increasing the ratio of thiol to ene functional groupstoichiometry results in an increase in the overall functional groupconversion. Additionally, by incorporating more thiol content into thereaction, additional chain transfer in the step growth propagation isprevalent and results in further delayed gelation and reduced shrinkagestress.

The methacrylate-thiol-ene system exhibits a polymerization mechanismthat is a combination of both step and chain growth polymerizations(Cramer et al., 2009; Reddy et al., 2006; Lee et al., 2007). Due to theunique combination of both step and chain growth polymerizations, theoptimum thiol:ene ratio deviates from the traditional 1:1 stoichiometry.Increasing the thiol:ene stoichiometry results in systems withequivalent flexural modulus, 6-20% reduced flexural strength, 5-33%reduced shrinkage stress, and up to 70% reduced shrinkage stressrelative to traditional methacrylate resin systems such as ethoxylatedbisphenol-A dimethacrylate/triethylene glycol dimethacrylate(EBPADMA/TEGDMA).

Employing thiol-enes as reactive diluents results in systems thatexhibit the advantageous properties of both methacrylate and thiol-enesystems. Due to the strong homopolymerization tendency of methacrylatefunctional groups, the early stages of the reaction are dominated bymethacrylate homopolymerization, resulting in further decreasedshrinkage stress due to the thiol-ene component acting as a diluent (Leeet al., Macromolecules 40(5):1473-1479, 2007; Cramer et al., 2009).

Additionally, use of the thiol-ene as the reactive diluent replacesTEGDMA, which is prone to leaching as well as typically providingrelatively high hydrophilicity. The methacrylate-thiol-ene resin systemsexhibit equivalent mechanical properties for flexural modulus andflexural strength, equivalent curing rates, increased overall functionalgroup conversion, and reduced shrinkage stress relative to thedimethacrylate control systems (Cramer et al., 2009).

The methacrylate-thiol-ene resin systems of the disclosure exhibitequivalent mechanical properties for flexural modulus and flexuralstrength, equivalent curing rates, increased overall functional groupconversion, and reduced shrinkage stress relative to the dimethacrylatecontrol systems (Cramer et al., 2009).

The disclosure provides a methacrylate-thiol-ene polymer resin systemwhich comprises a methacrylate monomer, a thiol monomer and an enemonomer. In one embodiment, the methacrylate monomer is present in atleast 50 wt % relative to the total weight of all polymerizablemonomers. In another embodiment, the combined weight of the thiolmonomer and the ene monomer is at least 10 wt % relative to the weightof all polymerizable monomers. In another embodiment, the resin systemcomprises 50 to 80% by weight of the methacrylate monomer and 20 to 50%by weight of the combined weight of the thiol and ene monomers;preferably 60 to 70% by weight of the methacrylate monomer and 30 to 40%by weight of the combined weight of the thiol and ene monomers, relativeto the total weight of all polymerizable monomers. In themethacrylate-thiol-ene polymer resin systems, the molar ratio of thiolfunctional groups from the thiol monomer relative to the ene functionalgroups from the ene monomer is greater than about 1:1; preferablygreater than about 2:1.

In one aspect, the methacrylate monomer is a dimethacrylate monomer. Ina specific aspect, the methacrylate monomer is EBPADMA. In anotheraspect, the thiol monomer is a multithiol monomer. In a specific aspect,the thiol monomer is PETMP which has four thiol functional groups permolecule as shown in FIG. 1. In a further aspect, the ene monomer is amulti-ene monomer. In a specific aspect, the ene monomer has three enefunctional groups per molecule. In another specific aspect, the enemonomer is selected from TMPTN or TATATO.

In specific aspects, the methacrylate-thiol-ene polymer resin system isselected from EBPADMA/PETMP/TATATO or EBPADMA/PETMP/TMPTN. In oneaspect, the weight ratio of methacrylate monomer to the combined weightof the thol and ene monomer is selected from 70/30 or 60/40. In anotherspecific aspect, the molar ratio of thiol functional groups to enefunctional groups is selected from 3:1, or 2:1.

Methacrylate-thiol-ene resin systems may also include and/or utilizevarious initiators, fillers, inhibitors and accelerators depending onthe application.

In one embodiment, the free radical initiated photopolymerization may bephotoinitiated by any light wavelength range within the ultraviolet(about 200 to about 400 nm) and/or visible light spectrum (about 380 toabout 780 nm). The choice of the wavelength range can be determined bythe photoinitiator employed. In one aspect, a full spectrum lightsource, e.g. a quartz-halogen xenon bulb, may be utilized forphotopolymerization. In another aspect, a wavelength range of about 320to about 500 nm is employed for photopolymerization.

In one embodiment, the resin further comprises a polymerizationphotoinitiator. In one aspect, any radical photoinitiator may beemployed. In another aspect, a photoinitiator responsive to visiblelight is employed. In a one aspect, the photoinitiator is a bis acylphosphine oxide (BAPO). In a specific aspect, the BAPO photoinitiator isphenyl bis(2,4,6-trimethyl benzoyl) phosphine oxide (Irgacure 819,Ciba). In another aspect, the photoinitiator is a metallocene initiator.In a specific aspect, the mettallocene initiator is Bis9eta5-2,4-cyclopentadien-1-yl)Bis[2,6-difluoro-3-(1H-pyrrol-1-yl)phenyl]titanium (Irgacure 784, Ciba).In another aspect, if photopolymerization using visible light isdesired, camphorquinone (CQ) may be used as an initiator, in combinationwith an accelerator, such as, for example, ethyl 4-dimethylaminobenzoate(EDAB). Alternatively, if ultraviolet (UV) photopolymerization isdesired, then an appropriate UV light activated photoinitiator may beemployed. For example, the photoinitiator can be selected from analpha-hydroxyketone, such as 1-hydroxy-cyclohexyl-phenylketone (Irgacure184, Ciba); a benzyldimethyl-ketal, such as2,2-dimethoxy-2-phenylacetophenone (DMPA, e.g. Irgacure 651, Ciba), or anumber of other commercially available photoinitiators may be used as aninitiator. Photoinitiators can be used in amounts ranging from about0.01 to about 5 weight percent (wt %). In one specific embodiment, 0.25wt % (2,4,6-trimethyl benzoyl) phosphine oxide (Irgacure 819) is used asthe photoinitiator. In another specific embodiment, 0.3 wt % CQ is usedas an initiator for visible light experiments, along with 0.8 wt % ethyl4-(dimethylamino)benzoate (commonly known as EDMAB or EDAB). In anotherspecific embodiment, 0.2 wt % DMPA is used as an initiator for UVpolymerization.

In one embodiment, one or more accelerators are utilized in thephotopolymerization. Amine accelerators may be used as polymerizationaccelerators, as well as other accelerators. Polymerization acceleratorssuitable for use are the various organic tertiary amines well known inthe art. In visible light curable compositions, the tertiary amines aregenerally acrylate derivatives such as dimethylaminoethyl methacrylateand, particularly, diethylaminoethyl methacrylate (DEAEMA), EDAB and thelike, in an amount of about 0.05 to about 0.5 wt %. The tertiary aminesare generally aromatic tertiary amines, preferably tertiary aromaticamines such as EDAB, 2-[4-(dimethylamino)phenyl]ethanol,N,N-dimethyl-p-toluidine (commonly abbreviated DMPT),bis(hydroxyethyl)-p-toluidine, triethanolamine, and the like. Suchaccelerators are generally present at about 0.5 to about 4.0 wt % in thepolymeric component. In one embodiment, 0.8 wt % EDAB is used in visiblelight polymerization.

In one embodiment, the resin compositions of the disclosure furthercomprise one or more fillers. In one aspect, fillers are used toincrease the viscosity of the dental restorative material, to tailor thehydrophilicity of the dental impression material, and to increase thestiffness (rubbery modulus) of the cured impression. The filledcompositions can include one or more of the inorganic fillers currentlyused in dental restorative materials, the amount of such filler beingdetermined by the specific function of the filled materials. Thus, forexample, in one aspect dental impression materials may be mixed with oneor more inorganic filler compounds such as barium, ytterbium, strontium,zirconia silicate and/or amorphous silica to match the color and opacityto a particular use or tooth. The filler can be a silanized filler. Thefiller is typically in the form of particles with a size ranging from0.01 to 5.0 micrometers. In one aspect, the filler is a hydrophobicfumed silica. In one specific aspect, the hydrophobic fumed silicafiller is composed of nanoparticles or nanoclusters. A nanoparticle isdefined as any particle less than 100 nanometers (nm) in diameter. Ananocluster is an agglomeration of nanoparticles. In one aspect,utilization of nanoclusters in a nanosized filler can be exploited toincrease the load and improve some mechanical properties. Other suitablefillers are known in the art, and include those that are capable ofbeing covalently bonded to the impression material itself or to acoupling agent that is covalently bonded to both. Examples of suitablefilling materials include but are not limited to, barium glass,ytterbium nanoglasses and nanoclusters, fumed silica, silica, silicateglass, quartz, barium silicate, strontium silicate, barium borosilicate,strontium borosilicate, borosilicate, lithium silicate, lithium aluminasilicate, amorphous silica, ammoniated or deammoniated calcium phosphateand alumina, zirconia, tin oxide, and titania. Some of theaforementioned inorganic filling materials and methods of preparationthereof are disclosed in U.S. Pat. No. 4,544,359 and U.S. Pat. No.4,547,531; pertinent portions of each of which are incorporated hereinby reference. In one aspect, the filler is a mixture of barium glass,ytterbium nanoglasses and nanoclusters, and fumed silica. In onespecific aspect, the filler is 85 wt % 0.5 micron barium glass, 10 wt %ytterbium 40 nm nanoglass and nanoclusters, 2.5 wt % Aerosil fumedsilica, and 2.5 wt % Cabosil fumed silica. In another aspect, the filleris a mixture of 90% 0.4 μm Schott glass and 10 wt % Aerosol OX-50. Theabove described filler materials may be combined with the resins of thedisclosure to form a dental composite material with high strength alongwith other beneficial physical and chemical properties.

In one aspect, suitable fillers are those having a particle size in therange from about 0.01 to about 5.0 micrometers, mixed with a silicatecolloid of about 0.001 to about 0.07 micrometers. The filler may beutilized in the filled resin compositions of the disclosure in theamount of from about 40 wt % to about 90 wt %; preferably about 60 wt %to 85 wt %; more preferably about 70 wt % to about 80 wt % of the totalweight of the composition. In one specific aspect, 72.5 wt % filler isutilized in the filled resin composition. In another specific aspect, 60wt % filler is utilized in the filled resin composition.

In another embodiment, the resin composition further comprises apolymerization inhibitor, or stabilizer. Examples of inhibitors includehydroquinone monomethyl ether (MEHQ),aluminum-N-nitrosophenylhydroxylamine, and2,6-di-tertbutyl-4-methylphenol (BHT). In a specific aspect, theinhibitor is aluminum-N-nitrosophenylhydroxylamine (Q1301, Wako PureChemical, Osaka, Japan). The optional inhibitor may be utilized in theamount of from about 0.001 wt % to about 0.5 wt %, or about 0.01 wt % toabout 0.1 wt % of the resin composition. In one specific aspect, theinhibitor aluminum-N-nitrosophenylhydroxylamine is utilized as 0.035 wt% of the resin. In another specific aspect,aluminum-N-nitrosophenylhydroxylamine is utilized at 0.075 wt % of thetotal weight of the filled resin composition.

In one aspect, the resin composition further comprises a UV absorber.The UV absorber can be selected from, for example,5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid, Uvinul® 3000 fromBASF Corp., and other various benzophenones, e.g. UV-5411 from AmericanCyanamid. The UV absorber can be present in from about 0.05 to about 5wt %; preferably less than about 0.5 wt % of the weight of the totalweight of the filled composition. In one specific aspect, Uvinul® 3000is present in 0.10 wt % of the total weight of the filled composition.

The disclosure provides a new resin system for use in dental restorativematerials. The polymerizable resin system comprises a methacrylatemonomer, a thiol monomer, and an ene monomer. In one aspect, themethacrylate is present from about 40 wt % to about 90 wt %, preferablyabout 50 wt % to about 80 wt %, more preferably about 60 wt % to about70 wt % of the total weight of the unfilled resin. In another aspect,the combined weight of the thiol and ene components are from about 10 wt% to about 60 wt % of the unfilled resin, preferably about 20 wt % toabout 50 wt %, more preferably about 30 wt % to about 40 wt % of thetotal weight of the unfilled resin. In one aspect, the molar ratio ofthiol to ene functional groups in the resin composition is greater thanabout 1:1; preferably greater than about 1.5:1; more preferably greaterthan about 1.75:1; more preferably greater than about 2:1.

In one embodiment, the resin composition further comprises aphotoinitiator. In optional aspects, the resin further comprises afiller. In another embodiment, the thiol-ene-methacrylate resin furthercomprises an inhibitor.

The disclosure provides a range of visible light curedmethacrylate-thiol and methacrylate-thiol-ene systems. In one aspect,relative to the BisGMA/TEGDMA control resin, methacrylate-thiol-enesystems exhibit equivalent cure speed and up to 24% increasedmethacrylate functional group conversion for the EBPADMA/PETMP:TATATOsystem and up to 17% increased methacrylate functional group conversionfor the EBPADMA/PETMP:TMPTN system. In another aspect, increasing thethiol-ene content or thiol to ene ratio increases the overall functionalgroup conversions.

In one aspect, the increased functional group conversion improves thebiocompatibility of the methacrylate-thiol-ene systems as dentalrestorative materials. In a specific aspect, the ternary systems exhibitdecreased cytotoxicity when compared to dimethacrylate resin systems.

In one aspect, in the methacrylate-thiol-ene systems, increasing thethiol to ene stoichiometric ratio in both the systems containing eitherene TATATO or TMPTN reduces shrinkage stress without compromisingflexural modulus. However, flexural strength is slightly reduced. In themethacrylate-thiol-ene systems, increasing the thiol-ene content from 30to 40% resulted in further reductions in shrinkage stress. However, inthe EBPADMA/PETMP:TATATO unfilled system there was also a significantdrop in both flexural modulus and flexural strength. In theEBPADMA/PETMP:TMPTN unfilled system, increasing the thiol-ene contentfrom 30 to 40% did not significantly impact flexural modulus orstrength. Relative to the EBPADMA/TEGDMA control, theEBPADMA/PETMP:TATATO system exhibits up to 47% reduced shrinkage stressand is achieved without significant reductions in flexural modulus orstrength. In the EBPADMA/PETMP:TMPTN system, up to 72% reduced shrinkagestress is achieved without significantly reducing flexural modulus orstrength.

In another aspect, the methacrylate-thiol-ene systems exhibit equivalentpolymerization kinetics and increased overall functional groupconversion, along with reduction in shrinkage stress while maintainingequivalent flexural modulus and near equivalent flexural strengthrelative to the control dimethacrylate resins. In this aspect, thecombination of equivalent flexural modulus and reduced shrinkage stressin methacrylate-thiol-ene systems results in composites with superiorcharacteristics relative to composites comprising traditionaldimethacrylate resin systems.

In one specific aspect, the methacrylate-thiol-ene filled resincomposite system contains Ethoxylated Bis-Phenol A Dimethacrylate(EBPADMA) 14.891 wt %; Pentaerythritol Tetra(3-mercaptopropionate)(PETMP) 7.428 wt %; Triallyl Triazine Trione (TATATO) 2.519 wt %;aluminum N-nitrosophenylhydroxylamine 0.010 wt %; Uvinul 3000 0.100 wt%; Irgacure 819 0.075 wt %; Schott Glass 8235 0.4 μm 9.4% Sil 59.982 wt%; Ytterbium Glass SG-YBF 40-4-3% Sil 11.247 wt %; and Aerosil OX 50PA-Sil 3.749 wt %.

In another specific aspect, the methacrylate-thiol-ene filled resincomposite system contains Ethoxylated Bis-Phenol A Dimethacrylate(EBPADMA) 14.895 wt %; Pentaerythritol Tetra(3-mercaptopropionate)(PETMP) 5.923 wt %; trimethylolpropane trinorbornene 3.998 wt %;aluminum N-nitrosophenylhydroxylamine 0.010 wt %; Uvinul 3000 0.100 wt%; Irgacure 819 0.075 wt %; Schott Glass 8235 0.4 μm 9.4% Sil 59.999 wt%; Ytterbium Glass SG-YBF 40-4-3% Sil 11.250 wt %; and Aerosil OX 50PA-Sil 3.750 wt %.

In a further embodiment, the disclosure provides methacrylate-thiolresin systems which exhibit reduced shrinkage stress relative to thedimethacrylate controls. The methacrylate-thiol resin systems compriseone or more methacrylate monomers and one or more thiol monomers. In oneaspect, in the methacrylate-thiol systems the methacrylate is present inat least 50 wt % of the weight of all polymerizable monomers and thebalance of polymerizable monomers are thiol monomers. In another aspect,the thiol monomer is present in from about 1 wt % to about 50 wt %;preferably about 10 wt % to about 30 wt % of the total weight ofpolymerizable monomers in the methacrylate-thiol resin system.

In one embodiment, the filled resin is utilized as a photocurable dentalrestorative material. The photocurable restorative materials can be soldin separate syringes or single-dose capsules of different shades. Ifprovided in a syringe, the user dispenses (by pressing a plunger orturning a screw adapted plunger on the syringe) the necessary amount ofrestorative material from the syringe onto a suitable mixing surface.Then the material is placed directly into the cavity, mold, or locationof use. If provided as a single-dose capsule, the capsule is placed intoa dispensing device that can dispense the material directly into thecavity, mold, etc. After the restorative material is placed, it isphotopolymerized or cured by exposing the restorative material to theappropriate light source. The resulting cured polymer may then befinished or polished as necessary with appropriate tools. Such dentalrestoratives can be used for direct anterior and posterior restorations,core build-ups, splinting and indirect restorations including inlays,onlays and veneers.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” Accordingly,unless indicated to the contrary, the numerical parameters set forth inthe following specification and attached claims are approximations thatmay vary depending upon the desired properties sought to be obtained bythe present invention. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of theclaims, each numerical parameter should at least be construed in lightof the number of reported significant digits and by applying ordinaryrounding techniques.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contain certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements.

It will be clear that the systems and methods described herein are welladapted to attain the ends and advantages mentioned as well as thoseinherent therein. Those skilled in the art will recognize that themethods and systems within this specification may be implemented in manymanners and as such is not to be limited by the foregoing exemplifiedembodiments and examples.

While various embodiments have been described for purposes of thisdisclosure, various changes and modifications may be made which are wellwithin the scope of the present invention.

EXAMPLES

Experimental work on the methacrylate-thiol-ene polymer embodiments asdental restorative materials was performed to demonstrate thefeasibility and advantages of these polymers over currently used dentalrestorative materials. Values in parenthesis in all Tables representstandard deviations.

Materials.

Dicyclopentadiene, trimethylolpropane triacrylate, and phenothiazine(PTZ) were purchased from Aldrich and utilized for norbornene monomersynthesis. The monomer triallyl-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione(TATATO) was also purchased from Aldrich. The photoinitiator Irgacure819 was donated by Ciba Specialty Chemicals (Tarrytown, N.Y.). Theinhibitor aluminum N-nitrosophenylhydroxylamine (Q1301) was donated byWako Pure Chemicals (Osaka, Japan). The monomers2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl] propane (BisGMA),ethoxylated bisphenol-A dimethacrylate (EBPADMA), and triethylene glycoldimethacrylate (TEGDMA) were donated by Esstech Inc. (Essington, Pa.).Pentaerythritol tetra(3-mercaptopropionate) (PETMP) was donated by EvansChemetics (Waterloo, N.Y.). All chemicals were used as received. Thenorbornene monomer trimethylolpropane tri-(norborn-2-ene-5-carboxylate)(TMPTN) was synthesized by a procedure that is described elsewhere(Cramer et al., 2009; Carioscia et al., Journal of Polymer Science PartA: Polymer Chemistry, 45(23): 5686-5696, 2007). Chemical structures ofmonomers are shown in FIG. 1. The inorganic glass filler is comprised of0.4 μm glass, or 0.5 μm barium glass from Schott (Elmsford, N.Y.),ytterbium 40 nm nanoglass and nanoclusters, Aerosil OX-50, and Cabosilfumed silicas were donated by Septodont, Confi-Dental Division(Louisville, Colo.).

Methods.

All analyses were conducted using 0.3 wt % Irgacure 819 as thephotoinitiator and were irradiated with 29 mW/cm² of light with an EXFOActicure (Mississauga, Ontario, Canada) with 400-500 nm filter.Irradiation intensity was measured at the sample surface level with anInternational Light, Inc. Model IL1400A radiometer (Newburyport, Mass.).

Flexural Modulus and Strength.

Samples were prepared using teflon molds measuring 2 mm×2 mm×25 mm andwere cured under identical conditions as in the FTIR analysis. Polymerflexural strength and modulus were calculated using a 3-point flexuraltest, carried out with a hydraulic universal test system (858 MiniBioix, MTS Systems Corporation, Eden Prairie, Minn., USA) using a spanwidth of 10 mm and a crosshead speed of 1 mm/min. For each system, atleast five duplicates were evaluated.

Fourier Transform Infrared Spectroscopy (FTIR).

Kinetic analysis was conducted using a Nicolet 750 Magna FTIRspectrometer (Madison, Wis.) with a KBr beam splitter and an MCT/Adetector. Series scans were recorded at a rate of approximately 2 scansper second until the reaction was complete, as indicated by thefunctional group absorption peak no longer decreasing. Experiments wereconducted in the near infrared (7000-4000 cm⁻¹) with samples placedbetween glass slides with a 1.0 mm glass spacer. Methacrylate functionalgroup conversion was monitored utilizing the methacrylate absorptionpeak at 6164 cm⁻¹ and the allyl ether absorption peak at 6132 cm⁻¹.Methacrylate and allyl ether peak absorbances are overlapped in the nearinfrared and a Gaussian fitting peak deconvolution method was utilizedto determine individual functional group conversions. The near infraredconfiguration is preferred when evaluating dental resins due to the 1 mmsample thickness that is more relevant to a clinical curing thickness.Norbornene functional groups do not exhibit a strong enough absorptionin the near infrared to determine functional group conversion. For eachcomposition, experiments were performed in triplicate.

Shrinkage Stress.

Experiments were performed with a tensometer (American DentalAssociation Health Foundation), which monitors stress development usingcantilever beam deflection theory. A detailed description of thetensometer and measurement technique is found elsewhere (Lu et al.,Dental Materials, 21(12), 2005, 1129-1136). Simultaneous conversionmeasurements are facilitated using remote near infrared transmittedthrough the polymer sample via fiber optic cables. Samples are placedbetween 6 mm glass rods and measured 1.5 mm in thickness. Irradiationintensity is measured at the tip of the 6 mm glass rod. As this diameteris less than the diameter of the radiometer detector, the measuredintensity of 29 mW/cm² is less than the actual irradiation intensity.For each composition, experiments were performed in triplicate.

Example 1 Polymerization Kinetics & Conversion

Polymerization kinetics were monitored for variousmethacrylate-thiol-ene, methacrylate-thiol and dimethacrylate controlresins under identical curing conditions. All samples contained 0.3 wt %Irgacure 819, 0.035 wt % Q1301, and were irradiated at 29 mW/cm² with a400-500 nm filter. Conversion of functional groups was monitored byFTIR.

Functional group conversion data over time in various systems areillustrated in FIGS. 2-4. Final conversion for each system is shown inTable 1. FIG. 2 shows methacrylate conversion monitored over time forfour resin systems. Two methacrylate control systems BisGMA/TEGDMA andEBPADMA/TEGMA, both at a 70/30 wt ratio, were compared to twomethacrylate-thiol-ene systems: EBPADMA/PETMP:TATATO at 70 wt %methacrylate/30 wt % thiol-ene with a 2:1 stoichiometric ratio of thiolto ene functional groups and EBPADMA/PETMP:TMPTN at 70/30 wt ratio witha 2:1 stoichiometric ratio of thiol to ene functional groups. Themethacrylate-thiol-ene systems exhibited more complete methacrylateconversion than the control methacrylate systems.

FIG. 3 shows both methacrylate and ene (ene) functional group conversionutilizing a methacrylate-thiol-ene system with EBPADMA/PETMP:TATATO, ina 70/30 weight percent of methacrylate (EBPADMA) to thiol:ene(PETMP:TATATO). The 1:1; 2:1 and 3:1 ratios represent the molar ratio ofthiol (PETMP) to ene (TATATO) functional groups. The off-stoichiometricsystems contain the same overall weight percent of thiol-ene resin, butthe ratio of thiol to ene functional groups is 2:1, or 3:1 compared tothe traditional 1:1 ratio of thiol to ene functional groups that isoptimum for a step growth system. As the ratio of thiol to enefunctional groups is increased in the EBPADMA/PETMP:TATATO 70/30 system,the ene functional group conversion increases from 45% for the 1:1system to 61% for the 3:1 system. Methacrylate functional groupconversion also increases slightly from 92% to 95%.

FIG. 4 shows methacrylate functional group conversion utilizing amethacrylate-thiol-ene system with EBPADMA/PETMP:TMPTN, in a 70/30weight percent of methacrylate (EBPADMA) to thiol:ene (PETMP:TMPTN). The1:1; 2:1 and 3:1 ratios represent the molar ratio of thiol (PETMP) toene (TMPTN) functional groups. The EBPADMA/PETMP:TMPTN system alsoexhibited increased methacrylate functional group conversion as thethiol-ene ratio and content were increased. Norbornene functional groupconversions were not resolvable. Kinetic results in FIGS. 2-4demonstrate near equivalent polymerization rates for all of the systemsthat were evaluated.

Table 1 shows the methacrylate-thiol-ene systems all exhibit increasedfunctional group conversion relative to the control dimethacrylatesystems. The off-stoichiometric systems contain the same overall weightpercent of thiol-ene resin, but the molar ratio of thiol to enefunctional groups is 3:2, 2:1, or 3:1 rather than the traditional 1:1molar ratio of thiol to ene functional groups that is optimum for a stepgrowth system. In the EBPADMA/PETMP:TATATO 60/40 system (60 wt %methacrylate/40 wt % thiol-ene), both 2:1 and 3:1 molar ratios of thiolto ene functional groups were examined and conversion of bothmethacrylate and ene functional groups was found to be higher than forthe 70/30 system. The methacrylate-thiol-ene systemsEBPADMA/PETMP:TATATO, and EBPADMA/PETMP:TMPTN exhibited equivalent orgreater cure speed with higher overall conversion relative to thedimethacrylate BisGMA/TEGDMA and EBPADMA/TEGDMA control systems.

TABLE 1 Final conversions for BisGMA/TEGDMA, EBPADMA/TEGDMA,EBPADMA/PETMP:TATATO, and EBPADMA/PETMP:TMPTN systems. Wt % Thiol:EneMeth Ene Meth/ group Conversion Conversion Formulation Thiol:Ene molRatio (%) (%) BisGMA/ — — 60 (1) — TEGDMA 70/30 EBPADMA/ — — 71 (1) —TEGDMA 70/30 EBPADMA/ 70/30 1:1 92 (1) 45 (1) PETMP:TATATO 3:2 93 (1) 53(1) 2:1 95 (1) 60 (1) 3:1 94 (1) 61 (5) EBPADMA/ 60/40 2:1 96 (1) 70 (3)PETMP:TATATO 3:1 98 (1) 81 (3) EBPADMA/ 70/30 1:1 79 (1) — PETMP:TMPTN2:1 88 (1) — 3:1 86 (1) — EBPADMA/ 60/40 2:1 88 (1) — PETMP:TMPTN

Example 2 Flexural Modulus and Strength

Methacrylate conversion and mechanical properties of cured resins weretested for methacrylate-thiol-ene, methacrylate-thiol resin systems anddimethacrylate control resins when subjected to identical curingconditions. Relative monomer amounts are shown in Table 2 for eachsample. All samples contained 0.3 wt % Irgacure 819, 0.035 wt % Q1301,and were irradiated at 29 mW/cm² with a 400-500 nm filter for 150seconds.

Results for flexural modulus and strength for methacrylate,methacrylate-thiol, and methacrylate-thiol-ene systems are shown inTable 2. The EBPADMA/PETMP 80/20 system exhibited an equivalent flexuralmodulus to BisGMA/TEGDMA and a slightly increased flexural modulusrelative to EBPADMA/TEGDMA. The flexural strength is slightly reducedrelative to both control systems. Increasing the PETMP content to 25percent resulted in a decrease in both flexural modulus and strength.The EBPADMA/PETMP:TATATO system with a 1:1 thiol:ene stoichiometryexhibited equivalent flexural modulus and strength relative to theEBPADMA/TEGDMA control resin. Increasing the thiol:ene stoichiometry inthe 70/30 EBPADMA/PETMP:TATATO system did not have a significant effecton the flexural modulus and slightly reduces the flexural strength.Increasing the thiol-ene content to 40% (EBPADMA/PETMP:TATATO 60/40)significantly reduced both flexural modulus and flexural strength forthe 2:1 system and results in dramatic reductions for the 3:1 system.The EBPADMA/PETMP:TMPTN 70/30 system with 1:1 thiol:ene stoichiometryexhibited equivalent flexural modulus and strength relative to theBisGMA/TEGDMA control resin. Increasing the thiol:ene ratio did not havea statistically significant effect on the flexural modulus and slightlyreduces the flexural strength. Increasing the thiol-ene content to 40%(EBPADMA/PETMP:TMPTN 60/40, 2:1) resulted in a system with an equivalentflexural modulus with a slightly reduced flexural strength relative toEBPADMA/TEGDMA.

TABLE 2 Conversion and flexural modulus and strength data formethacrylate-thiol- ene and methacrylate-thiol systems and methacrylatecontrol systems. Methacrylate/ Thiol:Ene Methacrylate Flexural FlexuralThiol:Ene Molar Conversion Modulus Strength Formulation Monomers WtRatio Ratio (%) (GPa) (MPa) BisGMA/TEGDMA 100/0  — 58 (1) 2.0 (0.1) 84(1) EBPADMA/TEGDMA 100/0  — 71 (1) 1.7 (0.1) 71 (2) EBPADMA/PETMP 80/201:0 86 (1) 2.1 (0.1) 69 (2) EBPADMA/PETMP 75/25 1:0 93 (1) 1.5 (0.1) 53(1) EBPADMA/PETMP:TATATO 70/30 1:1 72 (1) 1.8 (0.1) 71 (3) 3:2 79 (1)1.7 (0.1) 67 (4) 2:1 82 (1) 1.6 (0.2) 62 (4) 3:1 86 (1) 1.6 (0.2) 57 (2)EBPADMA/PETMP:TATATO 60/40 2:1 87 (1) 1.2 (0.3) 45 (3) 3:1 93 (1) 0.4(0.1) 24 (2) EBPADMA/PETMP:TMPTN 70/30 1:1 73 (1) 2.0 (0.2) 79 (5) 2:181 (1) 1.7 (0.1) 69 (1) 3:1 81 (1) 1.9 (0.2) 64 (2) EBPADMA/PETMP:TMPTN60/40 2:1 84 (1) 1.8 (0.1) 64 (2)

Flexural strength and flexural modulus for several systems is showngraphically in FIG. 4 and FIG. 5, respectively. System A and B representcontrol methacrylate systems, system C is a methacrylate/thiol system,and systems D-G are methacrylate-thiol-ene systems. Monomers utilized ineach resin system are shown in Table 3. Methacrylate-thiol-ene systemsexhibited flexural strength and flexural modulus properties approachingthose of the methacrylate control systems.

TABLE 3 Resin Systems used in Flexural Strength and Modulus Experimentsshown in FIGS. 4 and 5. Weight Thiol:ene System Monomers Ratio mol ratioA BisGMA/TEGMA 70/30 NA B EBPADMA/TEGDMA 70/30 NA C EBPADMA/PETMP 75/25NA D EBPADMA/PETMP:TATATO 70/30 3:1 E EBPADMA/PETMP:TMPTN 70/30 2:1 FEBPADMA/PETMP:TMPTN 70/30 3:1 G EBPADMA/PETMP:TMPTN 60/40 3:1

Example 3 Shrinkage Stress

Various resin system samples were subjected to identical curingconditions with a 400-500 nm filter and 29 mW/cm measured by radiometerthrough 6 mm glass rods. Shrinkage stress of cured resins was measuredfor methacrylate-thiol-ene, methacrylate/thiol and dimethacrylatecontrol resins when subjected to identical curing conditions.

Results for shrinkage stress and methacrylate conversion are shown inTable 4. The irradiation intensity for shrinkage stress is measuredthrough the tip of 6 mm glass rods. As such, the actual irradiationintensity is greater than the measured intensity and the samples achievehigher conversion than for flexural or kinetic measurements. TheEBPADMA/PETMP systems both exhibited reduced shrinkage stress relativeto the control resins with stress decreasing with increased thiolcontent. The EBPADMA/PETMP:TATATO 70/30 systems all exhibit reducedshrinkage stress as compared to the control resins. As the thiol to enefunctional group ratio is increased from 1:1 to 3:1 the shrinkage stressis further reduced from 2.1 to 1.4 MPa. The EBPADMA/PETMP:TATATO 60/40systems exhibit even greater reductions in shrinkage stress than the70/30 systems. However, these unfilled resin systems also exhibitsignificant reductions in flexural modulus and strength (Table 2). TheEBPADMA/PETMP:TMPTN systems also exhibit reduced shrinkage stressrelative to the control resins. For the 70/30 systems, the shrinkagestress ranges from 1.8 to 1.4 MPa as the thiol to ene functional groupratio increases from 1:1 to 3:1. The EBPADMA/PETMP:TMPTN 60/40 systemwith a 2:1 ratio of thiol to norbornene functional groups exhibits thelowest shrinkage stress (for a system without a significant reduction inflexural modulus and strength) at 1.0 MPa.

Results for shrinkage stress and methacrylate conversion fordimethacrylate control resins and methacrylate/thiol systems aregraphically illustrated in FIG. 7. Results for shrinkage stress andmethacrylate conversion for various methacrylate-thiol-ene systemscompared to dimethacrylate control systems are shown in FIGS. 8 and 9.

TABLE 4 Polymerization shrinkage stress and functional group conversion.Methacrylate/ Thiol:Ene Thiol:Ene Methacrylate Shrinkage Formulation WtRatio Mol Ratio Conversion (%) Stress (MPa) BisGMA/ 70/30 — 73 (5) 3.3(0.4) TEGDMA EBPADMA/ 70/30 — 82 (2) 3.8 (0.2) TEGDMA EBPADMA/ 80/20 1:097 (1) 1.9 (0.2) PETMP 75/25 1:0 98 (1) 1.4 (0.2) EBPADMA/ 70/30 1:1 86(1) 2.1 (0.1) PETMP: 3:2 94 (1) 2.0 (0.2) TATATO 2:1 96 (1) 1.9 (0.1)3:1 98 (1) 1.4 (0.1) EBPADMA/ 60/40 2:1 97 (1) 1.3 (0.1) PETMP: 3:1 99(1) 1.0 (0.1) TATATO EBPADMA/ 70/30 1:1 87 (1) 1.8 (0.1) PETMP: 2:1 90(1) 1.4 (0.1) TMPTN 3:1 92 (2) 1.5 (0.1) EBPADMA/ 60/40 2:1 94 (1) 1.0(0.1) PETMP: TMPTN

Example 4 Methacrylate-Thiol-Ene Filled Composites as Dental RestorativeMaterials

Various methacrylate-thiol-ene systems were prepared and evaluatedrelative to dimethacrylate controls. The BisGMA/TEGDMA andEBPADMA/TEGDMA control resins were 70/30 weight percent mixtures. TheEBPADMA/PETMP-TATATO resins also contained 70 percent methacrylate(EBPADMA) by weight. The PETMP and TATATO were included at varyingstoichiometric ratios: 1:1, 2:1, and 3:1. Each resin included 0.035 wt %Q1301 and 0.3 wt % Irgacure 819. The resins were filled with 72.5 wt %fillers that were 90% Schott 0.4 μm glass and 10 wt % aerosol OX-50. Thecomposites were mixed with a Flacktek Speedmixer (DAC 150 FVZ, FlacktekInc, Landrum S.C.). Photocuring was performed with a Maxima Pure Powerdental lamp.

The methacrylate-thiol-ene systems were evaluated and compared todimethacrylate controls. In both cases the primary component (70 wt %)was the dimethacrylate and the reactive diluent was a thiol-enecomponent. For the thiol-ene component, 1:1, 2:1, and 3:1 stoichiometricratios of thiol to ene functional groups were evaluated in otherwiseequivalent composites.

All resins systems were filled to same consistency with inorganic glassfiller. The consistency was based on a method in which 3.5 kg of weightis placed on a sample of consistent size for 3 minutes and produces aflattened sample with a diameter of, in this case, 31 mm. Thisconsistency value was chosen in order to make the composites clinicallyrelevant in terms of handling. The methacrylate-thiol-ene resins containapproximately 72.5 wt % inorganic glass filler. The control resins arefilled with 73.5 wt % for BisGMA/TEGDMA and 76 wt % for EBPADMA/TEGDMA.

Depth of Cure.

A cylindrical mold 6 mm long and 4 mm in diameter is filled with thecomposite resin and cured for 20 seconds from one end. The uncuredmaterial is then removed and the cured specimen is measured in fivelocations with a micrometer accurate to 0.01 mm and these values areaveraged. The averaged value is then divided by two to obtain the depthof cure. The procedure is performed according to ISO 4049-7.10,incorporated herein by reference.

Flexural Strength and Modulus.

Six molds are prepared in the dimension 2 mm×2 mm×25 mm and are storedin 37±1° C. distilled water for 24±2 hours. The molds are then brokenusing a universal materials testing machine (Instron 4411, Instron,Norwood Mass.). The procedure is performed according to ISO 4049-7.11,incorporated herein by reference.

Fourier Transform Infrared Spectroscopy (FTIR).

Experiments were utilized for functional group conversion and conductedin the near infrared (7000-4000 cm⁻¹) using a Nicolet 6700 FTIRspectrometer (Madison, Wis.) with a XT-KBr beam splitter and a DTGS KBrdetector. Samples were placed between two thin plastic films and twoglass slides with a sample thickness of 2 mm. Functional groupconversions were monitored utilizing the methacrylate absorption at 6164cm-1 and the allyl ether absorption peak at 6132 cm-1. A Gaussianfitting peak deconvolution method was utilized to determine theindividual functional group conversion. For each system, six trials wereperformed.

Volumetric Shrinkage.

A small sample of material is placed on the detector of a linometer(ACTA, Amsterdam) and cured for 40 seconds. The linear shrinkage is thenrecorded for an additional ten minutes and the linear shrinkage value atthe end of testing is multiplied by three to approximate volumetricshrinkage of the composite. A minimum of three trials are conducted foreach material.

Polymerization Stress.

A tensometer (American Dental Association Health Foundation) detectsstress development using cantilever beam theory. A cylindrical sample 6mm in diameter and 1.5 mm thick is irradiated for 40 seconds and thestress profile is monitored for an additional 20 minutes. A minimum ofthree trials are conducted.

Water Absorption and Solubility.

Five cylindrical molds are prepared 15 mm in diameter and 1 mm thick.Specimens are maintained in a dessicator at 37±1° C. until a constantweight is recorded (ml). The physical dimensions are recorded and thespecimens are then immersed in distilled water maintained at 37±1° C.for seven days. The molds are then blotted dry and air dried for 15seconds before being weighed (m2). The specimens are then returned tothe dessicator at 37±1° C. until a constant weight is again reached(m3). Water sorption (W_(sp)) and water solubility (W_(sl)) are thencalculated according to equations 1 and 2.

$\begin{matrix}{W_{sp} = \frac{{m\; 2} - {m\; 3}}{V}} & {{Equation}\mspace{14mu} 1} \\{W_{sp} = \frac{{m\; 1} - {m\; 3}}{V}} & {{Equation}\mspace{14mu} 2}\end{matrix}$

V is equal to the volume of each specimen, calculated from thedimensions recorded. The procedure is performed according to ISO4049-7.12, incorportated herein by reference.

Mechanical Properties.

Flexural strength and modulus were evaluated for each of the compositesystems. Results are given in Table 5. All of the systems exhibit higherflexural strength than the control composites. The flexural modulus ishighest for the 1:1 system and decreases for the 2:1 and 3:1 systems.The flexural modulus is higher for all three of the ternarymethacrylate/thiol-ene systems than the control systems.

TABLE 5 Flexural properties of control and experimental systems.Flexural Flexural Thiol:Ene Strength Modulus Formulation Ratio (MPa)(GPa) BisGMA/TEGDMA / 102 (7) 7.2 (0.7) EBPADMA/TEGDMA / 114 (5) 7.7(0.3) EBPADMA/PETMP:TATATO 1:1  145 (11) 9.2 (0.9) EBPADMA/PETMP:TATATO2:1 146 (8) 8.8 (0.8) EBPADMA/PETMP:TATATO 3:1 150 (9) 8.2 (1.0)

Depth of Cure.

The calculated depth of cure for each material after 20 seconds of lightcuring is shown in Table 6.

TABLE 6 Depth of cure after 20 sec light curing. Thiol:Ene Depth ofFormulation Ratio Cure (mm) BisGMA/TEGDMA / 2.15 (0.04) EBPADMA/TEGDMA /2.26 (0.03) EBPADMA/PETMP:TATATO 1:1 2.53 (0.04) EBPADMA/PETMP:TATATO2:1 2.62 (0.03) EBPADMA/PETMP:TATATO 3:1 2.63 (0.06)The depth of cure is increased over the control systems for the ternarymethacrylate/thiol-ene systems. There is not much significant differencebetween the depth of cure values for the three experimental systems.

C═C Conversion.

The methacrylate function group conversion of the materials was measuredfor each of the samples tested for flexural modulus and strength. Table7 shows the methacrylate and allyl ether conversion. The methacrylateconversion for the ternary systems is increased over the conversion forthe methacrylate controls. The allyl ether conversion increasessignificantly in the ternary systems as the ratio of thiol-to-ene isincreased in favor of the thiol monomer.

TABLE 7 Functional group conversion. Methacrylate Ene Thiol:EneConversion Conversion Formulation Ratio (%) (%) BisGMA/TEGDMA / 54 (1) /EBPADMA/TEGDMA / 59 (1) / EBPADMA/PETMP:TATATO 1:1 69 (1) 17 (2)EBPADMA/PETMP:TATATO 2:1 72 (2) 29 (2) EBPADMA/PETMP:TATATO 3:1 74 (1)35 (3)

Volumetric Shrinkage.

The shrinkage determined with the linometer for each material is shownin Table 8. The volume shrinkage for the 1:1 systems is notstatistically different from the controls, but as the ratio ofthiol-to-ene is increased, the shrinkage decreases.

TABLE 8 Volumetric shrinkage. Thiol:Ene Volumetric Formulation RatioShrinkage (%) BisGMA/TEGDMA / 2.35 (0.03) EBPADMA/TEGDMA / 2.49 (0.08)EBPADMA/PETMP:TATATO 1:1 2.27 (0.10) EBPADMA/PETMP:TATATO 2:1 2.03(0.07) EBPADMA/PETMP:TATATO 3:1 1.84 (0.17)

Shrinkage Stress.

The polymerization stress for each system is shown in Table 9. Theternary methacrylate/thiol-ene systems show approximately a 20-30%reduction in shrinkage stress compared to the control systems.

TABLE 9 Shrinkage stress. Thiol:Ene Shrinkage Formulation Ratio Stress(MPa) BisGMA/TEGDMA / 2.19 (0.04) EBPADMA/TEGDMA / 2.28 (0.04)EBPADMA/PETMP:TATATO 1:1 1.70 (0.11) EBPADMA/PETMP:TATATO 2:1 1.78(0.16) EBPADMA/PETMP:TATATO 3:1 1.52 (0.25)

Water Sorption and Solubility.

Table 10 shows the results for the water sorption and solubility of thematerials. There is a significant decrease in both water sorption andsolubility for the thiol-ene systems compared to the BisGMA/TEGDMAcontrol and a slight decrease in both properties from the EBPADMA/TEGDMAcontrol. There does not seem to be a significant trend in the propertieswhen the amount of thiol in the ternary systems is increased.

TABLE 10 Water sorption and solubility. Water Water Thiol:Ene SorptionSolubility Formulation Ratio (μg/mm³) (μg/mm³) BisGMA/TEGDMA / 30.3(0.6) 5.1 (0.4) EBPADMA/TEGDMA / 15.2 (0.7) 3.1 (1.2)EBPADMA/PETMP:TATATO 1:1 13.5 (1.6) 0.3 (0.8) EBPADMA/PETMP:TATATO 2:111.9 (1.3) −0.9 (0.9)   EBPADMA/PETMP:TATATO 3:1  13 (1.2) −0.8 (0.5)  

Example 5 Other Filler Compositions for Methacrylate-Thiol-Ene FilledComposites

Staring with a resin composition comprising methacrylate/thiol:ene at a60/40 wt ratio of methacrylate to thiol-ene component and a 2:1 molarratio of thiol to ene functional groups. Two methacrylate-thiol-enesystems were evaluated: EBPADMA/PETMP:TATATO (alpha formulation inFigures) and EBPDMA/PETMP:TMPTN (beta formulation in Figures) resinswere utilized in the following filler experiments. Filler powders werevaried according to the following protocol. All formulations contain acombined 95 wt % of Schott 0.5 micron barium glass and Ytterbium 40 nmnanoglass and nanoclusters. All formulations also contained a combined 5wt % of Aerosil and Cabosil fumed silica fillers. All testedcombinations are shown in Table 11.

TABLE 11 Fillers in Methacrylate-Thiol-Ene Composite. wt % of powder wt% Formulation schott ytterbium aerosil cabosil filled A1 80 15 5.0 0.076.8 A2 80 15 0.0 5.0 75.9 A3 80 15 2.5 2.5 76.1 B1 85 10 5.0 0.0 76.1B2 85 10 0.0 5.0 74.5 B3 85 10 2.5 2.5 75.8 C1 90 5.0 5.0 0.0 76.5 C2 905.0 0.0 5.0 75.8 C3 90 5.0 2.5 2.5 75.2

The composites were filled to attain a certain consistency, but all hadsimilar filling percentages. The composites were compounded as follows.Mixing was performed in a Flacktek centrifugal mixer. Powders were mixedtogether in a bag and added slowly to a mixing jar containing the resinsolution. Approximately ¼ of the powders were added and then mixed,another ¼ were added and mixed, another ¼ were added and mixed. The restof the powders are added in small portions in order to achieve thedesired consistency and not make the composite too thick.

The composites were cured with a dental lamp: visible light (400-500 nm)at about 400 mW/cm². The cure times were different for each test asfollows:

a. Depth of cure—20 sec;

b. Microhardness, Flexural, Compressive, DTS, Conversion—40 sec eachside; and

c. Volume Shrinkage—40 sec.

Results for selected EBPADMA/PETMP:TATATO (alpha) and EBPDMA/PETMP:TMPTN(beta) filled cured resins are shown in FIGS. 10-12. FIG. 10 showsresults for flexural strength. There were no statistical differences inflexural strength between filler powder formulations for each resinformulation, or between the resin formulations. FIG. 11 shows fillerformulation A2 exhibited a lower flexural modulus in both resinformulations. There was also a different flexural modulus between resinformulations for the A1 formulation. There was little difference inflexural modulus for A3, B2, C2 for either alpha or beta resinformulation. FIG. 12 shows microhardness results for selectedformulations. Although there was some variation in microhardness betweendifferent powder formulations, there was no statistical differencebetween resin formulations with the same powder formulations.

Further data for EBPADMA/PETMP:TATATO (alpha) filled composites at a60/40 wt ratio of methacrylate to thiol-ene component and a 2:1 molarratio of thiol to ene functional groups are shown in Tables 12 and 13below.

TABLE 12 Filler Optimization Data for EBPADMA/PETMP:TATATO 60/40, 2:1.Consistency Depth of Flexural Flexural (3.5 kg, Cure Micro- StrengthModulus Filler 3 min) (mm) hardness (MPa) (MPa) A1 22 × 22 2.86 55.2(4.0) 124 (9) 8094 (176) A2 17 × 17 2.52 45.6 (2.4) 111 (6) 7582 (401)B2 19 × 20 2.24 46.7 (2.7)  118 (10) 8592 (573) C2 18 × 18 2.81 52.0(2.2)  121 (15) 8972 (183) A3 24 × 24 2.26 48.4 (2.6)  126 (14) 8687(415) B3 26 × 26 2.07 47.3 (1.4) 155 (8) 9188 (747) C3 25 × 26 2.43 46.3(1.4) 152 (7) 9525 (318) B1 29 × 30 2.32 51.0 (2.2) 147 (8) 9238 (273)C1 28 × 28 2.63 51.2 (2.9)  141 (11) 8727 (327)

TABLE 13 Filler Optimization Data for EBPADMA/PETMP:TATATO 60/40, 2:1.Compressive Strength DTS C═C Conversion Filler (MPa) (MPa) OverallMethacrylate Allyl Ether A1 299 (22) 55 (6) 78 (1)   83 (1) 43 (1) A2222 (47) 50 (3) 78 (<1)   83 (<1) 46 (1) B2 293 (34) 44 (4) 78 (1)    83 (<1) 48 (1) C2 305 (22) 53 (5) 75 (1)   81 (1) 45 (3) A3 233 (24)59 (4) 79 (1)   84 (1) 46 (1) B3 339 (30) 64 (5) 78 (<1)   82 (<1) 51(1) C3 288 (18) 68 (1) 78 (<1)   83 (<1) 54 (3) B1 293 (36) 62 (4) 77(<1) 81 (1) 49 (3) C1 333 (35) 54 (3) 77 (<1) 81 (1)   49 (<1)

Example 6 Biocompatibility Study

In vitro mammalian cell culture studies have been used historically toevaluate cytotoxicity of biomaterials and medical devices (Wilsnack, etal., Biomaterials, medical Devices and Artificial Organs 1: pp. 543-562(1973)). A cytotoxicity study was used to evaluate the biocompatibilityof a test article extract using an in vitro mammalian cell culture test.This study was based on the requirements of the InternationalOrganization for Standardization 10993: Biological Evaluation of MedicalDevices, Part 5: in vitro Methods.

Test articles were extracted with single strength Minimal EssentialMedium supplemented with 5% serum and 2% antibiotics. (1×MEM). Articleswere extracted based upon the USP ratio for material thickness greaterthan or equal to 0.5 mm, a ratio of 60 cm²:20 mL extraction vehicle. Thetest and control articles were extracted at 37° C. for 24 hours using1×MEM to simulate physiological conditions. The test/control article wasdiscarded. The extracts were evaluated in the following assay.

A number of controls were used to evaluate the assay performance. Forthe Negative Control, high density polyethylene was prepared and asingle preparation of the material was extracted using the sameconditions as uses for the test article. A Reagent Control was a singlealiquot of the extraction vehicle without test material was prepared andtreated using the same conditions as described for the test article. APositive Control of tin stabilized polyvinylchloride, the current NAMSApositive control vehicle, was prepared using same ratio of test articleto extraction vehicle.

Mammalian cell culture monolayer, L-929, mouse fibroblast cells, (ECACCCatalog No. 85103115), were used. L-929 cells were propagated andmaintained in open wells containing single strength Minimum EssentialMedium supplemented with 5% serum and 2% antibiotics (1×MEM) in agaseous environment of 5% carbon dioxide (CO₂). For this study, 10 cm²wells were seeded, labeled with passage number and date, and incubatedat 37° C. in 5% CO₂ to obtain sub-confluent monolayers of cells prior touse. Aseptic procedures were used in the handling of the cell culturesfollowing approved NAMSA Standard Operating Procedures.

Each culture well was selected which contained a sub-confluent cellmonolayer. The growth medium in triplicate cultures was replaced with 2mL of the test extract. Similarly, triplicate cultures were replacedwith 2 mL of the reagent, negative and positive control extracts. Eachwell was labeled with the corresponding lab number, replicate number andthe dosing date and incubated at 37° C. in 5% CO₂ for 48 hours.

Following incubation, the cultures was examined microscopically (100×)to evaluate cellular characteristics and percent lysis. The color of thetest medium was observed. Each culture well was evaluated for percentlysis and cellular characteristics using the criteria shown in Table 14(United States Pharmacopeia, USP 31, National Formulary 26 Ch. 87.Biological Reactivity Tests, in vitro. (2008)). The reagent control andthe negative control had a reactivity of grade 0 and the positivecontrols were scored as a grade 3 or 4.

TABLE 14 USP Cytotoxicity Scoring. Grade Reactivity Conditions of allCultures 0 None Discrete intracytoplasmic granules; no cell lysis 1Slight Not more than 20% of the cells are round, loosely attached, andwithout intracytoplasmic granules; occasional lysed cells are present 2Mild Not more than 50% of the cells are round and devoid ofintracytoplasmic granules; no extensive cell lysis and empty arenabetween cells 3 Moderate Not more than 70% of the cell layers containrounded cells or are lysed 4 Severe Nearly complete destruction of thecell layers

The following samples were tested in this assay. Themethacrylate-thiol-resin resin systems and composite systems (filledresin systems) were not considered orally toxic based on the testconditions.

TABLE 15 Cytotoxicity Data for Resin and Composite Systems. ResinSystems Grade BisGMA/TEGDMA (70/30) 3 EBPADMA/PETMP:TATATO (80/20) 0EBPADMA/PETMP:TMPTN (70/30) 0 Composite Systems (75 wt % filled) 0EBPADMA/PETMP:TATATO (60/40, 2:1) (alpha system) 0 EBPADMA/PETMP:TMPTN(60/40, 2:1) (beta system) 0

1. A photopolymerizable dental restorative composition wherein thecomposition comprises, relative to the total weight of all polymerizablemonomers: at least about 40% by weight of a methacrylate monomer; and atleast about 10% by weight of combined weight of a thiol monomer and anene monomer; and wherein the molar ratio of thiol functional groups fromthe thiol monomer relative to the ene functional groups from the enemonomer is greater than about 1:1.
 2. The composition of claim 1 whereinthe molar ratio of the thiol functional groups to the ene functionalgroups is greater than about 1.5:1.
 3. The composition of claim 2wherein the molar ratio of the thiol functional groups to the enefunctional groups is greater than about 1.75:1.
 4. The composition ofclaim 3 wherein the molar ratio of the thiol functional groups to theene functional groups is greater than about 2:1.
 5. The composition ofclaim 1 further comprising a photoinitiator.
 6. The composition of claim5 wherein the photoinitiator is selected from one or more of a visiblelight activated photoinitiator, a UV light activated photoinitiator, ora combination thereof.
 7. The composition of claim 5 wherein thephotoinitiator is selected from (2,4,6-trimethyl benzoyl) phosphineoxide, camphorquinone, Bis9eta 5-2,4-cyclopentadien-1-yl)Bis[2,6-difluoro-3-(1H-pyrrol-1-yl)phenyl]titanium,1-hydroxy-cyclohexyl-phenylketone, and2,2-dimethoxy-2-phenylacetophenone.
 8. The composition of claim 5further comprising a polymerization accelerator.
 9. The composition ofclaim 5 further comprising a polymerization inhibitor.
 10. Thecomposition of claim 1, further comprising a filler in an amount of upto 90% by weight with respect to the total weight of the filledcomposition.
 11. The composition of claim 10 wherein the filler is 60 to85% by weight with respect to the total weight of the filledcomposition.
 12. The composition of claim 1 comprising 50 to 80% byweight of the methacrylate monomer; and 20 to 50% by weight of thecombined weight of the thiol monomer and the ene monomer.
 13. Thecomposition of claim 12 comprising 60 to 70% by weight of themethacrylate monomer; and 30 to 40% by weight of the combined weight ofthe thiol monomer and the ene monomer.
 14. The composition of claim 1wherein the methacrylate monomer is a dimethacrylate monomer.
 15. Thecomposition of claim 14 wherein the methacrylate monomer is selectedfrom ethylene glycoldi(meth)acrylate, ethoxylated bisphenol-Adimethacrylate (EBPADMA), tetraethyleneglycoldi(meth)acrylate (TEGDMA),poly(ethylene glycol) dimethacrylates, the condensation product ofbisphenol A and glycidyl methacrylate,2,2′-bis[4-(3-methacryloxy-2-hydroxy propoxy)-phenyl] propane (BisGMA),hexanediol di(meth) acrylate, tripropylene glycol di(meth)acrylate,butanediol di(meth)acrylate, neopentyl glycol di(meth)acrylate,diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate,dipropylene glycol di(meth)acrylate, allyl (meth)acrylate.
 16. Thecomposition of claim 15 wherein the methacrylate monomer is ethoxylatedbisphenol-A dimethacrylate (EBPADMA).
 17. The composition of claim 1wherein the thiol monomer is selected from one or more ofpentaerythritol tetramercaptopropionate (PETMP); 1-Octanethiol; Butyl3-mercaptopropionate; 2,4,6-trioxo-1,3,5-triazina-trig(triethyl-tris(3-mercapto propionate); 1,6-Hexanedithiol;2,5-dimercaptomethyl-1,4-dithiane, pentaerythritol tetramercaptoacetate,trimethylolpropane trimercaptoacetate, 2,3-dimercapto-1-propanol,2-mercaptoethylsulfide, 2,3-(dimercaptoethylthio)-1-mercaptopropane,1,2,3-trimercaptopropane, toluenedithiol, xylylenedithiol,1,8-octanedithiol, 1-hexanethiol and trimethylolpropanetris(3-mercaptopropionate), and glycol dimercaptopropionate.
 18. Thecomposition of claim 17 wherein the thiol monomer is pentaerythritoltetramercaptopropionate (PETMP).
 19. The composition of claim 1 whereinthe ene monomer comprises two or more ene functional groups.
 20. Thecomposition of claim 19 wherein the ene monomer is selected from one ormore of Triallyl-1,3,5-triazine-2,4,6-trione (TATATO); Triethyleneglycoldivinyl ether (TEGDVE); Trimethylolpropane diallyl ether; Dodecyl vinylether (DDVE); 1,6-heptadiyne; 1,7-octadiyne;bis-2,2-[4-(2-[norborn-2-ene-5-carboxylate]ethoxy)phenyl]propane(BPAEDN); 1,6-hexanediol di-(endo,exo-norborn-2-ene-5-carboxylate)(HDDN); trimethylolpropane tri-(norborn-2-ene-5-carboxylate) (TMPTN);pentaerythritoltri-(norborn-2-ene-5-carboxylate) (PTN3); pentaerythritoltetra-(norborn-2-ene-5-carboxylate) (PTN4); tricyclodecane dimethanoldi-(endo, exo-norborn-2-ene-5-carboxylate) (TCDMDN); anddi(trimethylolpropane)tetra-(norborn-2-ene-5-carboxylate) (DTMPTN). 21.The composition of claim 20 wherein the ene monomer is selected fromTriallyl-1,3,5-triazine-2,4,6-trione (TATATO) and trimethylolpropanetri-(norborn-2-ene-5-carboxylate) (TMPTN).
 22. A method of preparing ashaped dental prosthetic device for use in a human mouth, the methodcomprising: dispensing a photopolymerizable composition comprising,relative to the total weight of all polymerizable monomers: a. at leastabout 40% by weight of a methacrylate monomer; and b. at least about 10%by weight of combined weight of a thiol monomer and an ene monomer;wherein the molar ratio of thiol functional groups from the thiolmonomer relative to the ene functional groups from the ene monomer isgreater than about 1:1; c. a photoinitiator; and d. a filler; shapingthe composition into a form of the shaped dental prosthetic device; andphotopolymerizing the shaped composition.
 23. The method of claim 22,wherein the molar ratio of the thiol functional groups to the enefunctional groups is greater than about 1.5:1.
 24. A photopolymerizabledental restorative composition wherein the composition comprises,relative to the total weight of all polymerizable monomers: at leastabout 50% by weight of a methacrylate monomer; and wherein the balanceof the polymerizable monomers are thiol monomers.
 25. The composition ofclaim 24 further comprising a photoinitiator.